Although progress has been made in understanding the molecular basis of X- linked SCID and SCID associated with enzyme deficiencies, the molecular basis of most forms of SCID and the less severe syndromes of combined immune deficiency disease (CID) remains unknown. Over the past 15 years, Drs. Bart Haynes and Rebecca Buckley have acquired immune system tissues from 30 patients with various forms of primary immune deficiency diseases. The general goal of this project is to examine thymic and peripheral SCID and CID immune organ tissues for functional and molecular abnormalities, with studies especially centering on tissues from those patients that have forms of fatal SCID and CID for which there is no known cause. This will be accomplished by immunohistologic and light microscopic analysis of immune microenvironments, reverse transcriptase PCR analysis of tissues for cytokine and cytokine receptor mRNA expression, analysis of thymic epithelial (TE) and thymic fibroblast (TF) call lines derived from SCID and CID patients for cell surface molecule expression and cytokine production, and when appropriate, determine the nucleotide sequence of relevant abnormal genes.